Supracellular organization confers directionality and mechanical potency to migrating pairs of cardiopharyngeal progenitor cells.
Supracellular organization confers directionality and mechanical potency to migrating pairs of cardiopharyngeal progenitor cells.
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DOI：
10.7554/elife.70977
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发表时间：
2021-11-29
期刊：
影响因子：
7.7
通讯作者：
Mogilner A
中科院分区：
文献类型：
--
作者：
Bernadskaya YY;Yue H;Copos C;Christiaen L;Mogilner A
生理和病理形态发生事件涉及广泛的集体运动，这表明多细胞排列赋予有助于组织规模组织的生化和生物力学特性。 Ciona 心咽祖细胞提供了最简单的集体细胞迁移模型，当在腹侧表皮和躯干内胚层之间移动时，粘性双侧细胞对沿着先导-尾随迁移路径极化。我们使用细胞波茨模型来计算探测与迁移细胞对的形状和集体极性一致的力的分布。结合计算模型、共焦显微镜和分子扰动，我们将心咽祖细胞确定为维持细胞上极性的最简单的细胞集体，其突出力、细胞基质粘附和沿前导轴的基于肌球蛋白的回缩力的差异分布。 4D 模拟和实验观察表明，细胞间通讯有助于建立一个层次结构，使集体极性与迁移方向保持一致，正如在计算机和体内的三个或更多细胞中观察到的那样。我们的方法揭示了迁移集体的新特性：细胞对更持久，迁移距离更长，并且可能具有更高的准确性。模拟表明，当细胞对集体极化时，它们可以更有效地克服躯干内胚层的机械阻力。我们提出，心咽祖细胞的极化超细胞组织赋予了新兴的物理特性，决定了形态发生过程中与其环境的机械相互作用。
Physiological and pathological morphogenetic events involve a wide array of collective movements, suggesting that multicellular arrangements confer biochemical and biomechanical properties contributing to tissue-scale organization. The Ciona cardiopharyngeal progenitors provide the simplest model of collective cell migration, with cohesive bilateral cell pairs polarized along the leader-trailer migration path while moving between the ventral epidermis and trunk endoderm. We use the Cellular Potts Model to computationally probe the distributions of forces consistent with shapes and collective polarity of migrating cell pairs. Combining computational modeling, confocal microscopy, and molecular perturbations, we identify cardiopharyngeal progenitors as the simplest cell collective maintaining supracellular polarity with differential distributions of protrusive forces, cell-matrix adhesion, and myosin-based retraction forces along the leader-trailer axis. 4D simulations and experimental observations suggest that cell-cell communication helps establish a hierarchy to align collective polarity with the direction of migration, as observed with three or more cells in silico and in vivo. Our approach reveals emerging properties of the migrating collective: cell pairs are more persistent, migrating longer distances, and presumably with higher accuracy. Simulations suggest that cell pairs can overcome mechanical resistance of the trunk endoderm more effectively when they are polarized collectively. We propose that polarized supracellular organization of cardiopharyngeal progenitors confers emergent physical properties that determine mechanical interactions with their environment during morphogenesis.
影响因子：
3
作者：
Dehal PS;Boore JL
通讯作者：
Boore JL